1.Mechanism of Ethoxysanguinarine in Regulating IRE1/RIDD Signaling Pathway to Inhibit Endoplasmic Reticulum Stress and Alleviate Cardiomyocyte Apoptosis
Zucheng SHANG ; Hongzheng LI ; Mengfan LI ; Wen SUN ; Guosheng LIN ; Aling SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):141-148
ObjectiveTo investigate the effects of ethoxysanguinarine (ETH) on angiotensin Ⅱ (Ang Ⅱ)-mediated cardiomyocyte apoptosis and its regulatory effects of inositol-requiring enzyme 1 (IRE1)/regulated IRE1-dependent decay (RIDD) signaling pathway and endoplasmic reticulum stress. MethodsWestern blot was used to detect the establishment of the H9c2 model via Ang Ⅱ stimulation, which was identified as a cardiomyocyte apoptosis model. Subsequently, the inhibitory effect of ETH on cell proliferation was assessed using the cell counting Kit-8 (CCK-8) to determine the optimal effective dose of ETH. H9c2 cardiomyocytes were divided into a blank group, a model group (Ang Ⅱ, 1 mmol·L-1), and low-, medium-, and high-dose ETH groups (1.25, 2.5, and 5 mmol·L-1). Morphological changes in cardiomyocytes induced by Ang Ⅱ were detected using phalloidin staining. Cardiomyocyte apoptosis was assessed using terminal deoxynucleotidyl transferase dUTP nick and labeling (TUNEL) staining. The apoptosis cycle was detected by Annexin V/PI flow cytometry. Western blot was used to detect the expression levels of apoptosis-related proteins, endoplasmic reticulum stress, and IRE1/RIDD pathway-related proteins. ResultsWestern blot results showed that 1 mmol/mL Ang Ⅱ stimulation significantly increased the protein expression levels of Bip, p-IRE1, and Bid in H9c2 cells (P<0.05, P<0.01), indicating the induction of endoplasmic reticulum stress, activation of the IRE1/RIDD signaling pathway, and initiation of the apoptosis process. Compared with the blank group, the model group showed a significant increase in the surface area of H9c2 cells and the apoptosis rate of cardiomyocytes, as well as in both early and late apoptosis rates (P<0.01). The expression levels of Bid, Bax, cleaved-Caspase-3, and cleaved-Caspase-8 proteins were significantly increased, while the expression level of Bcl-2 protein was significantly decreased (P<0.01). The expression levels of Bip, p-IRE1, and p-RIDD proteins were significantly increased (P<0.05, P<0.01). Compared with those in the model group, the surface area of cardiomyocytes and the apoptosis rate of cardiomyocytes in all ETH groups were significantly decreased after drug intervention. Both early and late apoptosis rates were significantly decreased. The expression level of cleaved-Caspase-8 was significantly decreased in the low-dose ETH group (P<0.05). The expression levels of Bid, Bax, and cleaved-Caspase-8 were significantly decreased in the medium-dose ETH group (P<0.05, P<0.01). The high-dose ETH group significantly reduced the expression levels of Bid, Bax, cleaved-Caspase-3, and cleaved-Caspase-8 (P<0.05, P<0.01) and significantly increased the expression level of Bcl-2 (P<0.05). The level of p-IRE1 protein in the medium-dose ETH group was significantly decreased (P<0.01). The expression levels of Bip, p-IRE1, and p-RIDD proteins in the high-dose ETH group were significantly decreased (P<0.05, P<0.01). ConclusionETH can alleviate Ang Ⅱ-mediated cardiomyocyte apoptosis by inhibiting the IRE1/RIDD signaling pathway and further alleviate the cardiac injury caused by hypertension.
2.Mechanism of Ethoxysanguinarine in Regulating IRE1/RIDD Signaling Pathway to Inhibit Endoplasmic Reticulum Stress and Alleviate Cardiomyocyte Apoptosis
Zucheng SHANG ; Hongzheng LI ; Mengfan LI ; Wen SUN ; Guosheng LIN ; Aling SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):141-148
ObjectiveTo investigate the effects of ethoxysanguinarine (ETH) on angiotensin Ⅱ (Ang Ⅱ)-mediated cardiomyocyte apoptosis and its regulatory effects of inositol-requiring enzyme 1 (IRE1)/regulated IRE1-dependent decay (RIDD) signaling pathway and endoplasmic reticulum stress. MethodsWestern blot was used to detect the establishment of the H9c2 model via Ang Ⅱ stimulation, which was identified as a cardiomyocyte apoptosis model. Subsequently, the inhibitory effect of ETH on cell proliferation was assessed using the cell counting Kit-8 (CCK-8) to determine the optimal effective dose of ETH. H9c2 cardiomyocytes were divided into a blank group, a model group (Ang Ⅱ, 1 mmol·L-1), and low-, medium-, and high-dose ETH groups (1.25, 2.5, and 5 mmol·L-1). Morphological changes in cardiomyocytes induced by Ang Ⅱ were detected using phalloidin staining. Cardiomyocyte apoptosis was assessed using terminal deoxynucleotidyl transferase dUTP nick and labeling (TUNEL) staining. The apoptosis cycle was detected by Annexin V/PI flow cytometry. Western blot was used to detect the expression levels of apoptosis-related proteins, endoplasmic reticulum stress, and IRE1/RIDD pathway-related proteins. ResultsWestern blot results showed that 1 mmol/mL Ang Ⅱ stimulation significantly increased the protein expression levels of Bip, p-IRE1, and Bid in H9c2 cells (P<0.05, P<0.01), indicating the induction of endoplasmic reticulum stress, activation of the IRE1/RIDD signaling pathway, and initiation of the apoptosis process. Compared with the blank group, the model group showed a significant increase in the surface area of H9c2 cells and the apoptosis rate of cardiomyocytes, as well as in both early and late apoptosis rates (P<0.01). The expression levels of Bid, Bax, cleaved-Caspase-3, and cleaved-Caspase-8 proteins were significantly increased, while the expression level of Bcl-2 protein was significantly decreased (P<0.01). The expression levels of Bip, p-IRE1, and p-RIDD proteins were significantly increased (P<0.05, P<0.01). Compared with those in the model group, the surface area of cardiomyocytes and the apoptosis rate of cardiomyocytes in all ETH groups were significantly decreased after drug intervention. Both early and late apoptosis rates were significantly decreased. The expression level of cleaved-Caspase-8 was significantly decreased in the low-dose ETH group (P<0.05). The expression levels of Bid, Bax, and cleaved-Caspase-8 were significantly decreased in the medium-dose ETH group (P<0.05, P<0.01). The high-dose ETH group significantly reduced the expression levels of Bid, Bax, cleaved-Caspase-3, and cleaved-Caspase-8 (P<0.05, P<0.01) and significantly increased the expression level of Bcl-2 (P<0.05). The level of p-IRE1 protein in the medium-dose ETH group was significantly decreased (P<0.01). The expression levels of Bip, p-IRE1, and p-RIDD proteins in the high-dose ETH group were significantly decreased (P<0.05, P<0.01). ConclusionETH can alleviate Ang Ⅱ-mediated cardiomyocyte apoptosis by inhibiting the IRE1/RIDD signaling pathway and further alleviate the cardiac injury caused by hypertension.
3.Theoretical Research on the Detailed Classification of Traditional Chinese Medicine Visceral Syndrome Differentiation Based on Syndrome-Formula Correspondence
Liqiu YU ; Zhuien WANG ; Mengfan LI ; Chengye CHEN ; Jiayu ZHANG ; Yi YANG
Journal of Traditional Chinese Medicine 2025;66(14):1504-1507
The current classification methods for traditional Chinese medicine (TCM) visceral syndrome differentiation suffer from excessive generalization, which hinders their clinical application. Based on the analysis of the pattern of "one syndrome corresponding to multiple formulas", this paper focused on the principle of syndrome-formula correspondence, and proposed that formula-syndromes are the smallest units for refining visceral syndromes. By establishing the correspondence between formula-syndromes and visceral syndromes, this study aims to further clarify the refined categories of syndromes and their treatment patterns, providing a new perspective for the standardization and objectification of TCM syndromes.
4.Aging and perioperative brain health: Mechanisms, management, and future.
Peilin CONG ; Qian CHEN ; Qianqian WU ; Jing WANG ; Xinwei HUANG ; Qian ZHANG ; Zheping CHEN ; Huanghui WU ; Yuxin ZHANG ; Mengfan HE ; Zhouxiang LI ; Li TIAN ; Lize XIONG
Chinese Medical Journal 2025;138(19):2381-2398
Globally, over 300 million surgeries are performed each year, and more than 50% of surgeries involve patients aged 65 and older. Aging poses significant challenges to perioperative brain health, as the deterioration of brain structure and function increases susceptibility to postoperative neurological complications. Protecting perioperative brain health remains a worldwide clinical challenge. With senescence, the brain undergoes a progressive decline in homeostasis across various molecular, cellular, and regional functions. Anesthetics and surgical stimuli may accelerate the disruption of brain homeostasis and exacerbate age-related neurodegeneration. This review provides a framework for understanding how anesthesia and surgery can affect brain health in the aging population and contribute to postoperative neurological complications, with a particular focus on perioperative neurocognitive disorder.
5.A Personalized Predictor of Motor Imagery Ability Based on Multi-frequency EEG Features.
Mengfan LI ; Qi ZHAO ; Tengyu ZHANG ; Jiahao GE ; Jingyu WANG ; Guizhi XU
Neuroscience Bulletin 2025;41(7):1198-1212
A brain-computer interface (BCI) based on motor imagery (MI) provides additional control pathways by decoding the intentions of the brain. MI ability has great intra-individual variability, and the majority of MI-BCI systems are unable to adapt to this variability, leading to poor training effects. Therefore, prediction of MI ability is needed. In this study, we propose an MI ability predictor based on multi-frequency EEG features. To validate the performance of the predictor, a video-guided paradigm and a traditional MI paradigm are designed, and the predictor is applied to both paradigms. The results demonstrate that all subjects achieved > 85% prediction precision in both applications, with a maximum of 96%. This study indicates that the predictor can accurately predict the individuals' MI ability in different states, provide the scientific basis for personalized training, and enhance the effect of MI-BCI training.
Humans
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Imagination/physiology*
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Electroencephalography/methods*
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Brain-Computer Interfaces
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Male
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Female
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Adult
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Young Adult
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Brain/physiology*
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Movement/physiology*
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Motor Activity/physiology*
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Psychomotor Performance/physiology*
6.Application of quantitative electroencephalography in predicting post-stroke cognitive impairment
Wenxiao NIU ; Ying GAO ; Mengfan LI ; Zhen ZHANG ; Jinbiao ZHANG
International Journal of Cerebrovascular Diseases 2025;33(5):362-365
Post-stroke cognitive impairment (PSCI) is a common complication of stroke, which seriously affects the quality of life of patients. Therefore, early and accurate prediction of PSCI is crucial for implementing targeted intervention measures. Quantitative electroencephalography (qEEG), as a non-invasive and objective neurophysiological technique, can provide objective basis for early prediction and targeted intervention of PSCI during the critical period of 72 hours to 1 month after stroke onset. This article reviews the current application status of qEEG in predicting PSCI, aiming to provide theoretical basis for early identification of patients with high-risk PSCI.
7.Discussion on the effects of Shenshuaikang Enema on H/ R-induced senescence of NRK-52E cells based on P53/P21 pathway
Yu ZHANG ; Lizeyu LYU ; Yong LIN ; Lihua WU ; Mengfan YANG ; Anqi TANG ; Mingquan LI
International Journal of Traditional Chinese Medicine 2025;47(8):1103-1109
Objective:To investigate the effects and mechanism of Shenshuaikang Enema on hypoxia/reoxygenation (H/R) NRK-52E cells; To provide references for Shenshuaikang Enema to treat AKI.Methods:The H/R-induced NRK-52E cell model was established, and control group, model group, drug-containing serum group, drug-containing blood group +p53 agonist group, p53 agonist group, p53 inhibitor group were set up. Cell viability was detected by CCK8. The cell cycle distribution in each group was analyzed using flow cytometry, while cell senescence was assessed via β-galactosidase staining. The levels of IL-6, IL-1β, and TNF-α in the cell supernatant were evaluated using ELISA. Western Blot analyses were conducted to measure the protein expressions of p53, phosphorylated p53 (p-p53), and p21.Results:Compared with model group, NRK-52E cell vitality significantly increased in the drug-containing serum group and p53 inhibitor group ( P<0.01, P<0.05), S phase and G2/M phase percentage was significantly reduced ( P<0.01), β-galactoase staining decreased ( P<0.01), the levels of IL-1β, IL-6 and TNF-α decreased ( P<0.05, P<0.01), the protein expressions of p-p53 and p21 decreased ( P<0.01). Compared with the drug-containing serum group, NRK-52E cell vitality significantly decreased in the drug-containing serum+p53 agonist group and p53 agonist group ( P<0.01), S phase and G2/M phase percentage was significantly increased ( P<0.01), β-galactoase staining increased ( P<0.01), the levels of IL-1β, IL-6 and TNF-α increased ( P<0.01), the protein expressions of p-p53 and p21 increased ( P<0.01 or P<0.05). Conclusion:The drug-containing serum of Shenshuaikang Enema may promote cell proliferation, improve cell cycle arrest, inhibit pro-inflammatory and senescence related secretory phenotypes, and inhibit cell senescence by inhibiting p53/p21 signaling pathway, so as to promote H/ R-induced NRK-52E cell damage repair.
8.Design and establishment of a database for toxins and molecular mass spectra of drugs
Xuemeng LI ; Mengfan LI ; Junjie MA ; Bin XU ; Jie DU ; Wei YOU ; Jia CHEN ; Jianwei XIE ; Dongsheng ZHAO
Military Medical Sciences 2025;49(1):41-46
Objective To construct a database for molecular mass spectra of toxins and drugs in order to facilitate the management and retrieval of mass spectra for nerve agents,metabolites and other small molecules.Methods Requirement analysis and functional design were performed using software engineering methods.The Spec2Vec algorithm was used for vector representation of mass spectra,while SMILES molecular structures were vectorized using the extended connectivity fingerprint(ECFP).A data storage model integrating structured information and vector representations was established using the Milvus database.Similarity search of mass spectra and molecular structures was conducted via vector similarity comparison and the FlashEntropySearch algorithm.Results The constructed database of mass spectra encompassed over 400,000 entries from such sources as OCAD,NIST,MASSBANK,metabolic products,and natural products of TCM,which was capable of searching for similarities in mass spectra and molecular structures.On a standard server,similarity search of mass spectra took no more than 5 seconds,while that of molecular structures took no more than 1 second.Conclusion The system enables efficient management of complex mass spectra and provides rapid retrieval and comparison of mass spectra-related information through advanced vector indexing technology,offering robust data support and research tools for toxicology and pharmacology.
9.Development and validation of a nutrition-related genetic-clinical-radiological nomogram associated with behavioral and psychological symptoms in Alzheimer’s disease
Jiwei JIANG ; Yaou LIU ; Anxin WANG ; Zhizheng ZHUO ; Hanping SHI ; Xiaoli ZHANG ; Wenyi LI ; Mengfan SUN ; Shirui JIANG ; Yanli WANG ; Xinying ZOU ; Yuan ZHANG ; Ziyan JIA ; Jun XU
Chinese Medical Journal 2024;137(18):2202-2212
Background::Few evidence is available in the early prediction models of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer’s disease (AD). This study aimed to develop and validate a novel genetic-clinical-radiological nomogram for evaluating BPSD in patients with AD and explore its underlying nutritional mechanism.Methods::This retrospective study included 165 patients with AD from the Chinese Imaging, Biomarkers, and Lifestyle (CIBL) cohort between June 1, 2021, and March 31, 2022. Data on demographics, neuropsychological assessments, single-nucleotide polymorphisms of AD risk genes, and regional brain volumes were collected. A multivariate logistic regression model identified BPSD-associated factors, for subsequently constructing a diagnostic nomogram. This nomogram was internally validated through 1000-bootstrap resampling and externally validated using a time-series split based on the CIBL cohort data between June 1, 2022, and February 1, 2023. Area under receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to assess the discrimination, calibration, and clinical applicability of the nomogram.Results::Factors independently associated with BPSD were: CETP rs1800775 (odds ratio [OR] = 4.137, 95% confidence interval [CI]: 1.276-13.415, P = 0.018), decreased Mini Nutritional Assessment score (OR = 0.187, 95% CI: 0.086-0.405, P <0.001), increased caregiver burden inventory score (OR = 8.993, 95% CI: 3.830-21.119, P <0.001), and decreased brain stem volume (OR = 0.006, 95% CI: 0.001-0.191, P = 0.004). These variables were incorporated into the nomogram. The area under the ROC curve was 0.925 (95% CI: 0.884-0.967, P <0.001) in the internal validation and 0.791 (95% CI: 0.686-0.895, P <0.001) in the external validation. The calibration plots showed favorable consistency between the prediction of nomogram and actual observations, and the DCA showed that the model was clinically useful in both validations. Conclusion::A novel nomogram was established and validated based on lipid metabolism-related genes, nutritional status, and brain stem volumes, which may allow patients with AD to benefit from early triage and more intensive monitoring of BPSD.Registration::Chictr.org.cn, ChiCTR2100049131.
10.White matter hyperintensity penumbra
Tan LI ; Mengfan YE ; Xiuying CAI ; Qi FANG
International Journal of Cerebrovascular Diseases 2024;32(5):380-385
White matter hyperintensities (WMHs) are one of the main imaging biomarkers of cerebral small vessel disease (CSVD). With the development of neuroimaging technology, the WMH penumbra (WMH-P) has gradually become a research hotspot. WMH-P refers to the area of brain tissue microstructural integrity destruction or reduced blood flow perfusion around WMH lesions, which is not visible on conventional MRI sequences. It is not only a risk factor for the progression of WMHs, but also associated with clinical symptoms such as cognitive impairment and gait abnormalities in patients with CSVD, and is considered a new potential and reversible therapeutic target.

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